High rates of relapse to drug use after prolonged drug-free periods characterize the behavior of experienced heroin and cocaine users, and of people in dietary treatment who attempt to restrict the intake of high-fat palatable food. The behavioral and neurochemical events that contribute to these high relapse rates, however, are not well understood. Relapse can be induced in human subjects and laboratory animals by reexposure to the drug (or food) previously used, re-exposure to environmental cues paired with drug (or food) self-administration, and by exposure to environmental stressors. We are using different animal models of relapse to study brain systems and neurotransmitters involved in relapse induced by environmental stressors, conditioned drug (or food) cues and drug (or food) re-exposure in rats with a history of heroin, alcohol, methamphetamine, cocaine or palatable high-fat food self-administration.